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Colon cancer molecular subtypes identified by expression profiling and associatedto stroma, mucinous type and different clinical behavior

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  • Additional Information
    • Contributors:
      Fundación Mutua Madrileña; Fundación Científica AECC; Fundación Genoma España; Sociedad Española de Oncologia Médica; Instituto de Salud Carlos III; Asociación Española Contra el Cáncer; Sociedad Española de Oncología Médica
    • Publication Information:
      Springer Science and Business Media LLC, 2012.
    • Publication Date:
      2012
    • Abstract:
      BackgroundColon cancer patients with the same stage show diverse clinical behavior dueto tumor heterogeneity. We aimed to discover distinct classes of tumorsbased on microarray expression patterns, to analyze whether the molecularclassification correlated with the histopathological stages or otherclinical parameters and to study differences in the survival.MethodsHierarchical clustering was performed for class discovery in 88 colon tumors(stages I to IV). Pathways analysis and correlations between clinicalparameters and our classification were analyzed. Tumor subtypes werevalidated using an external set of 78 patients. A 167 gene signatureassociated to the main subtype was generated using the 3-Nearest-Neighbormethod. Coincidences with other prognostic predictors were assesed.ResultsHierarchical clustering identified four robust tumor subtypes withbiologically and clinically distinct behavior. Stromal components(p BRAFmutations. Tumor subtypes werevalidated using an external set of 78 patients. A 167 gene signatureassociated to the Low-stroma-subtype distinguished low risk patients fromhigh risk patients in the external cohort (Dukes B andC:HR = 8.56(2.53-29.01); Dukes B,C andD:HR = 1.87(1.07-3.25)). Eight different reported survival genesignatures segregated our tumors into two groups the Low-stroma-subtype andthe other tumor subtypes.ConclusionsWe have identified novel molecular subtypes in colon cancer with distinctbiological and clinical behavior that are established from the initiation ofthe tumor. Tumor microenvironment is important for the classification andfor the malignant power of the tumor. Differential gene sets and biologicalpathways characterize each tumor subtype reflecting underlying mechanisms ofcarcinogenesis that may be used for the selection of targeted therapeuticprocedures. This classification may contribute to an improvement in themanagement of the patients with CRC and to a more comprehensiveprognosis.
    • File Description:
      application/pdf
    • ISSN:
      1471-2407
    • Accession Number:
      10.1186/1471-2407-12-260
    • Rights:
      Springer TDM
      CC BY
    • Accession Number:
      edsair.doi.dedup.....9fa3ab8205469cc61a2c321942134829